Staphylococcus epidermidis biofilm formation on indwelling medical devices is frequently associated with the development of chronic infections. Nevertheless, it has been suggested that cells released from these biofilms may induce severe acute infections with bacteraemia as one of its major associated clinical manifestations. However, how biofilm-released cells interact with the host remains unclear. Here, using a murine model of hematogenously disseminated infection, we characterized the interaction of cells released from S. epidermidis biofilms with the immune system. Gene expression analysis of mouse splenocytes suggested that biofilm-released cells might be particularly effective at activating inflammatory and antigen presenting cells and inducing cellular apoptosis. Furthermore, biofilm-released cells induced a higher production of pro-inflammatory cytokines, in contrast to mice infected with planktonic cells, even though these had a similar bacterial load in livers and spleens. Overall, these results not only provide insights into the understanding of the role of biofilm-released cells in S. epidermidis biofilm-related infections and pathogenesis, but may also help explain the relapsing character of these infections.

Mentions:
As shown in Figure 2, mice infected with biofilm-released cells had significantly higher serum levels of the chemokines CCL3, CCL4, and CXCL1, as well as higher levels of TNF-α than mice infected with planktonic cells, 2 h after the bacterial challenge. At that time point, no differences were found in the levels of any assessed cytokines between biofilm and biofilm-released cells-infected mouse groups. In contrast, 6 h after infection, markedly higher serum levels of CXCL1, TNFα, and IL-6 were detected in mice infected with biofilm-released cells than in the biofilm cell-infected counterparts. By 14 h after infection, lower serum levels of CCL2 were detected in mice infected with biofilm-released cells, when compared with their planktonic infected counterparts. No significant differences were detected in the serum levels of any other assessed cytokine among the different infected groups.

Mentions:
As shown in Figure 2, mice infected with biofilm-released cells had significantly higher serum levels of the chemokines CCL3, CCL4, and CXCL1, as well as higher levels of TNF-α than mice infected with planktonic cells, 2 h after the bacterial challenge. At that time point, no differences were found in the levels of any assessed cytokines between biofilm and biofilm-released cells-infected mouse groups. In contrast, 6 h after infection, markedly higher serum levels of CXCL1, TNFα, and IL-6 were detected in mice infected with biofilm-released cells than in the biofilm cell-infected counterparts. By 14 h after infection, lower serum levels of CCL2 were detected in mice infected with biofilm-released cells, when compared with their planktonic infected counterparts. No significant differences were detected in the serum levels of any other assessed cytokine among the different infected groups.

Staphylococcus epidermidis biofilm formation on indwelling medical devices is frequently associated with the development of chronic infections. Nevertheless, it has been suggested that cells released from these biofilms may induce severe acute infections with bacteraemia as one of its major associated clinical manifestations. However, how biofilm-released cells interact with the host remains unclear. Here, using a murine model of hematogenously disseminated infection, we characterized the interaction of cells released from S. epidermidis biofilms with the immune system. Gene expression analysis of mouse splenocytes suggested that biofilm-released cells might be particularly effective at activating inflammatory and antigen presenting cells and inducing cellular apoptosis. Furthermore, biofilm-released cells induced a higher production of pro-inflammatory cytokines, in contrast to mice infected with planktonic cells, even though these had a similar bacterial load in livers and spleens. Overall, these results not only provide insights into the understanding of the role of biofilm-released cells in S. epidermidis biofilm-related infections and pathogenesis, but may also help explain the relapsing character of these infections.